Nuclear RNA surveillance of genome expression: From yeast to mammals

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The successful production of proteins from their gene blueprint (DNA) requires a key intermediate step in which a particular gene is selected by complex molecular machines and initially copied into a related RNA molecule called the transcript. However this process is far more complex than initially predicted as much of the RNA transcript does not directly encode protein and is referred to as non-coding RNA. Surprisingly gene transcripts are predominantly non-coding so that the protein coding portions must be joined together forming so called messenger RNA with the non-coding (intronic) RNA chopped out by a process called RNA splicing. Indeed splicing can occur in different ways so that many different messenger RNAs can be generated from just one initial RNA transcript. We have shown that non-coding RNA is first removed from the gene transcript before splicing occurs and at the same time that the transcript is being synthesised. Thus non-coding RNA can be sorted out and removed before critical splicing events take place. This seemingly wasteful mechanism is not only employed to help make the process of messenger RNA production more efficient and better regulated but is also used to completely degrade any messenger RNAs that might have protein coding defects. Removal of such mutant messenger RNAs is likely to be a critical quality control mechanism to prevent the synthesis of the wrong protein which in turn could have damaging effects on cell function. This mechanism is now given the name of Nuclear RNA Surveillance (NuRNASu). In the absence of this intricate quality control process cells will become deregulated leading to diseases such as cancer.